Hypoxia is one of the main hallmarks of hepatocellular carcinoma (HCC) resulting from improper oxygenation and insufficient nourishment of the HCC microenvironment. The effect of hypoxia is mediated by hypoxia-inducible factor-1A (HIF-1A) via targeting various downstream pathways, including glycolysis, angiogenesis, and survival signaling. However, HCC cell lines in a 2-dimensional (2D) setting do not resemble the metabolic signature of HCC.
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